التفاصيل البيبلوغرافية
| العنوان: |
Pomalidomide in combination with dexamethasone results in synergistic anti-tumour responses in pre-clinical models of lenalidomide-resistant multiple myeloma. |
| المؤلفون: |
Rychak, Emily, Mendy, Derek, Shi, Tao, Ning, Yuhong, Leisten, Jim, Lu, Ling, Miller, Karen, Narla, Rama K., Orlowski, Robert Z., Raymon, Heather K., Bjorklund, Chad C., Thakurta, Anjan, Gandhi, Anita K., Cathers, Brian E., Chopra, Rajesh, Daniel, Thomas O., Lopez‐Girona, Antonia |
| المصدر: |
British Journal of Haematology; Mar2016, Vol. 172 Issue 6, p889-901, 13p |
| مصطلحات موضوعية: |
MULTIPLE myeloma, DEXAMETHASONE, IMMUNOLOGICAL adjuvants, BORTEZOMIB, GENE expression, DRUG resistance |
| مستخلص: |
Pomalidomide is an IMiD® immunomodulatory agent, which has shown clinically significant benefits in relapsed and/or refractory multiple myeloma (rr MM) patients when combined with dexamethasone, regardless of refractory status to lenalidomide or bortezomib. (Schey et al, ; San Miguel et al, 2013; Richardson et al, 2014; Scott, ) In this work, we present preclinical data showing that the combination of pomalidomide with dexamethasone (PomDex) demonstrates potent anti-proliferative and pro-apoptotic activity in both lenalidomide-sensitive and lenalidomide-resistant MM cell lines. PomDex also synergistically inhibited tumour growth compared with single-agent treatment in xenografts of lenalidomide-resistant H929 R10-1 cells. Typical hallmarks of IMiD compound activity, including IKZF3 (Aiolos) degradation, and the downregulation of interferon regulatory factor (IRF) 4 and MYC, seen in lenalidomide-sensitive H929 MM cell lines, were also observed in PomDex-treated lenalidomide-resistant H929 MM cells. Remarkably, this resulted in strong, synergistic effects on the induction of apoptosis in both lenalidomide-sensitive and resistant MM cells. Furthermore, gene expression profiling revealed a unique differential gene expression pattern in PomDex-treated samples, highlighted by the modulation of pro-apoptotic pathways in lenalidomide-resistant cells. These results provide key insights into molecular mechanisms of PomDex in the lenalidomide-resistant setting. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
